The overall objective of this proposal is to study the lymphokines and their receptors on human lymphocytes. More specifically, the lymphokines that, including B cell growth factor, B cell Inducing factor, and gamma interferon that play unique function roles in human B cell proliferation and differentiation. Initially, it is intended to purified both BCGF and BIF to homogeneity. Subsequently, radiolabeled lymphokines will be used to study binding properties and cellular distribution of their receptors. In the second stage, monoclonal antibodies directed at epitopes of these lymphokines will be developed to facilitate the study of the specific biological effects of the lymphokines in a variety of in vitro systems and to probe the molecular nature of these receptors. Furthermore, through the binding-inhibition assay, monoclonal anti-receptor antibodies will be developed. Each lymphokine receptor's susceptibility to modulation as induced by anti-receptor antibodies, lymphokine binding, or/and monocytes will be determined. In addition, long term culture of normal human B lymphocytes will be developed as a source for the study of the activation and regulation of human B cell growth and differentiation. Gamma interferon have been reported recently to have a B cell differentiation factor activity. Our preliminary results indicated that this lymphokine can induce the B-CLL cells to differentiate into cytoplasmic Ig positive plamacytoid cells. With the recently developed monoclonal anti-gamma interferon antibodies & purified gamma interferon preparation, the effect of gamma interferon on normal B cell differentiation will also be pursued. With the availability of highly purified lymphokines, specific monoclonal anti-receptor and anti-lymphokine antibodies, and the long term cultured normal B cells, a precise deneation of the events that cause B cell differentiation will be attempted. Using B cells as a model, the studies proposed here would contribute to the understanding of cell differentiation and proliferation in other cellular systems, in particular the tumor cells.